Takashi Yanagida, Jun Tsushima, Yoshihisa Kitamura, Daijiro Yanagisawa, Kazuyuki Takata, Tomonori Shibaike, Atsuko Yamamoto, Takashi Taniguchi, Hiroyuki Yasui, Takahiro Taira, Shigehiro Morikawa, Toshihiro Inubushi, Ikuo Tooyama, Hiroyoshi Ariga, "Oxidative Stress Induction of DJ-1 Protein in Reactive Astrocytes Scavenges Free Radicals and Reduces Cell Injury", Oxidative Medicine and Cellular Longevity, vol. 2, Article ID 896932, 7 pages, 2009. https://doi.org/10.4161/oxim.2.1.7985
Oxidative Stress Induction of DJ-1 Protein in Reactive Astrocytes Scavenges Free Radicals and Reduces Cell Injury
Astrocytes, one of the predominant types of glial cells, function as both supportive and metabolic cells for the brain. Under cerebral ischemia/reperfusion-induced oxidative conditions, astrocytes accumulate and activate in the ischemic region. DJ-1 has recently been shown to be a sensor of oxidative stress in living cells. However, the function of astrocytic DJ-1 is still unknown. In the present study, to clarify the effect of astrocytic DJ-1 protein under massive oxidative insult, we used a focal ischemic rat model that had been subjected to middle cerebral artery occlusion (MCAO) and reperfusion. We then investigated changes in the distribution of DJ-1 in astrocytes, DJ-1 release from cultured astrocytes, and the effects of recombinant DJ-1 protein on hydrogen peroxide (H2O2)-induced death in normal and DJ-1-knockdown SH-SY5Y cells and on in vitro scavenging of hydroxyl radicals (•OH) by electron spin resonance spectrometry. At 24 h after 2-h MCAO and reperfusion, an infarct lesion was markedly observed using magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. In addition, reactive astrocytes enhanced DJ-1 expression in the penumbral zone of the ischemic core and that DJ-1 protein was extracellularly released from astrocytes by H2O2 in in vitro primary cultures. Although DJ-1-knockdown SH-SY5Y cells were markedly vulnerable to oxidative stress, treatment with glutathione S-transferase-tagged recombinant human DJ-1 protein (GST-DJ-1) significantly inhibited H2O2-induced cell death. In addition, GST-DJ-1 protein directly scavenged •OH. These results suggest that oxidative stress induces the release of astrocytic DJ-1 protein, which may contribute to astrocyte-mediated neuroprotection.
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